Wilson Disease (WD) is an autosomal recessive disorder of copper metabolism. Prospective screening for WD has been proposed however a sensitive and specific biochemical genetic assay was not available and primary molecular analysis was not feasible. WD may be the most frequent and most preventable cause of chronic liver disease in children. Wilson Disease is treatable and serious symptoms can be avoided if a diagnosis is made early. A recently developed ELISA assay using specific monoclonal antibody to ceruloplasmin has generated evidence that it provides the basis of a population screening assay for WD. Following a final validation, there are plans to commercialize this assay as a kit for population screening. Biochemical genetic screening assays generate a small protion of equivocal results and patients detected presymptomatically require confirmation. Genotyping provides an effective means by which to clarify equivocal results and confirm putativly affected patients. The WD gene, P-type ATPase ATP7B, contains common mutations however these are specific to given ethnic groups and patients are most often compond heterozygotes for a common mutation and a rare/private mutation. A 2-tiered genotyping assay is proposed. Common mutations (appropriate to the population assayed) are rapidly identified with specific assays using the LightCycler and SimpleProbe chemistry. Comprehensive gene scanning employs the newly developed dye binding/high resolution thermal denaturation platform to detect heteroduplex molecules. PCR is performed using rapid air-driven thermalcycling in the presence of the dsDNA binding dye LCGreen I. A unique property of LCGreen I is at concentrations saturating newly synthisized DNA, it does not inhibit PCR, a quality not shared by other dsDNA binding dyes. Following amplification, dye saturated PCR product is assayed by high resolution thermal denaturation. Analysis is homogeneous, performed in the PCR reaction capillary, with no post-PCR processing. Analysis requires approximately 90 seconds/specimen. Utilizing air driven PCR, LCGreen I, and high resolution thermal denaturation, the ATP7B gene, including coding and adjoining splice sites, is scanned for heteroduplexes in approximately 1.5 hours, which includes test specimens and controls. PCR products showing evidence of heteroduplexes are sequenced. Dye binding/high resolution denaturation provides an inexpensive and truly user-friendly platform for gene scanning by heteroduplex analysis. Prospective screening for WD improves efficacy of treatment and quality of life for affected patients. Genotyping is the best option to confirm results based upon ceruloplasmin analysis in asymptomatic patients.